Forming double layer-encapsulated quantum dots for bio-imaging and cell targeting

We report a simple and effective approach for the preparation of double layer-encapsulated quantum dots (DL-Qdots) composed of alkyl-capping ligands to interdigitate with hydrophobic, protective agents on the surface of AgInS2/ZnS quantum dots (Qdots), which allow phase transfer of hydrophobic Qdots from the organic phase into the aqueous phase. The alkyl-capping ligands consist of a hydrophobic, aliphatic chain and different functional terminal groups (e. g., carboxyl, amine, hydroxyl, and thiol groups) that can serve as reactive sites to chemically couple with other materials. The resulting DL-Qdots bearing various functional groups retain good fluorescence properties and show excellent solubility as well as stability over a range of pH in the aqueous phase. Cytotoxicity studies of DL-Qdots bearing carboxyl groups (DL-Qdots-COOH) were carried out against human cervical (HeLa) cancer cells to elicit no apparent toxicity even at high concentrations of 300 mu g mL(-1) and 24 h of incubation. To demonstrate their potential biomedical application, DL-Qdots-COOH were further conjugated with folate for staining in HeLa, human liver carcinoma (HepG2), and human breast (MCF-7) cancer cells. Confocal imaging characterization revealed that folate-conjugated DL-Qdots could target most specifically and effectively HeLa cells via folate receptor-mediated targeted delivery compared to HepG2 and MCF-7 cells. The generality and simplicity of this newly developed strategy can possibly be extended to a large variety of hydrophobic Qdots and nanocrystals whose surface protective agents have a long aliphatic chain.